Genetic Reconstitution of Autoimmune Type 1 Diabetes With Two Major Susceptibility Genes in the Rat
Bibliographic record
Abstract
The Komeda diabetes-prone (KDP) rat is an animal model of human autoimmune type 1 diabetes. We have previously shown that two major susceptibility genes, the major histocompatibility complex (MHC) RT1(u) haplotype and Cblb (Casitas B-lineage lymphoma b) mutation, are responsible for the development of diabetes in KDP rats, suggesting a two-gene model for development of the disease. To confirm the two-gene model, we produced a congenic strain carrying mutated Cblb alleles of the KDP rat on a non-KDP genetic background harboring the RT1(u) haplotype on its MHC. Despite the low incidence and delayed onset of diabetes, the congenic strain did develop the disease, indicating that type 1 diabetes can be reconstituted on a non-KDP genetic background with the RT1(u) haplotype and Cblb mutation. Similar to observations in KDP rats, the congenic strain showed insulitis and thyroiditis, symptoms of autoimmunity. The low incidence and delayed onset of the disease strongly suggest involvement of genetic modifiers; the congenic strain established in this study should be useful for the mapping and identification of such modifiers.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".